Rationally Designed Highly Potent NKT Cell Agonists with Different Cytokine Selectivity through Hydrogen-Bond Interaction

Journal of Medicinal Chemistry, Год журнала: 2024, Номер 67(15), С. 12819 - 12834

Опубликована: Июль 20, 2024

Synthetic α-galactosylceramide (αGalCer) and its analogues as powerful agonists for natural killer T (NKT) cell manipulation have received significant attention in immunotherapy adjuvant development. However, identifying new potent NKT agonists, especially those with Th1 selectivity that promote anticancer effects, remains a challenging task. In this work, we introduced sulfonamide group into the acyl chain of αGalCer to form additional hydrogen bonds intensify glycolipid/CD1d interaction. Two compounds

Язык: Английский

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Encouraging Solution to the Problem of Synthesizing Protein α‐Thioester

Chinese Journal of Chemistry, Год журнала: 2024, Номер 42(10), С. 1114 - 1120

Опубликована: Фев. 5, 2024

Comprehensive Summary Expressed protein ligation (EPL) provides a powerful tool to access large‐size proteins with precise structures. Existing methods for constructing the critical thioester EPL have predominantly relied on recombinant intein fusion expressed in Escherichia coli (E. ). Despite its applications, expression of derived from eukaryotic E. inherently suffers limited solubility, inactivity intein, premature hydrolysis and low yields. To overcome these obstacles, we present herein facile one‐flask synthesis inaccessible α‐thioester via SUMO‐protein‐intein (SPI) sandwich model. The utility SUMO enhances yield prevents simplifies purification process. internal Cys residues can be readily produced is compatible EPL‐desulfurization protocol used prepare complex proteins, which otherwise difficult obtain using traditional methods. Its has been highlighted through human granulocyte colony‐stimulating factor (G‐CSF).

Язык: Английский

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Efficient Chemical Synthesis and Folding of Mirror‐Image Tropomyosin Receptor Kinase A Using the Strategy of Removable Glycosylation Modification^†

Chinese Journal of Chemistry, Год журнала: 2024, Номер 42(19), С. 2316 - 2322

Опубликована: Май 22, 2024

Comprehensive Summary The strategy of removable glycosylation modification was used to overcome the low‐efficiency problem encountered in chemical synthesis mirror‐image D ‐version immunoglobulin (Ig)‐like domain tropomyosin receptor kinase A ( lgC TrkA ), a protein molecule needed for screening ‐peptide ligands targeting this cell membrane receptor. It found that O‐linked‐β‐ N ‐acetyl‐ ‐glucosamine (O‐GlcNAc) at Ser 312 , or 320 can significantly improve efficiency and folding, while O‐GlcNAc 330 showed barely any improvement. This study provides new example demonstrating power folding difficult‐to‐obtain proteins. also presents evidence different sites would affect promoted by strategy.

Язык: Английский

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Investigation of N-Glycan Functions in Receptor for Advanced Glycation End Products V Domain through Chemical Glycoprotein Synthesis

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(27), С. 18270 - 18280

Опубликована: Июнь 25, 2024

The receptor for advanced glycation end products (RAGE) plays a crucial role in inflammation-related pathways and various chronic diseases. Despite the recognized significance of N-glycosylation ligand-binding V domain (VD) RAGE, comprehensive understanding site-activity structure-activity relationships is lacking due to challenges obtaining homogeneous glycoprotein samples through biological expression. Here, we combined chemical chemoenzymatic approaches synthesize RAGE-VD its congeners with Asn3-glycosylation by incorporating precise N-glycan structures. Evaluation these revealed that, comparison other forms, α2,6-sialylated at Asn3 site results more potent inhibition HMGB1-induced nuclear factor-κB (NF-κB) expression RAGE-overexpressing cells. Hydrogen/deuterium exchange-mass spectrum analysis sialylated RAGE-VD-induced interaction region within HMGB1. Conversely, VD has negligible effects on RAGE-VD/S100B interactions. This study established an approach accessing homogeneously glycosylated explored modulatory interactions between ligand proteins.

Язык: Английский

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Efficient chemical synthesis of mirror-image DNA polymerase Dpo4 assisted by one-pot multi-segment condensation

Organic & Biomolecular Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

This study describes an efficient chemical synthesis method of d -Dpo4, a valuable enzymatic tool producing mirror-image DNAs, using one-pot multi-segment condensation strategy.

Язык: Английский

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Studies toward Chemical Synthesis of Homogeneously Glycosylated Interleukin-10

Chinese Journal of Organic Chemistry, Год журнала: 2025, Номер 45(3), С. 951 - 951

Опубликована: Янв. 1, 2025

Язык: Английский

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Anti-Herpes simplex virus type 1 activity of the Rohdea chinensis (Baker) N. Tanaka aqueous extracts

Journal of Ethnopharmacology, Год журнала: 2025, Номер unknown, С. 120024 - 120024

Опубликована: Май 1, 2025

Язык: Английский

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Microwave-assisted synthesis of highly sulfated mannuronate glycans as potential inhibitors against SARS-CoV-2

Organic & Biomolecular Chemistry, Год журнала: 2024, Номер 22(19), С. 3986 - 3994

Опубликована: Янв. 1, 2024

Sulfated mannuronate glycans with up to 17 sulfation sites were synthesized using a microwave-assisted approach and evaluated as inhibitors against SARS-CoV-2.

Язык: Английский

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Site‐selective construction of N‐linked glycopeptides through photoredox catalysis

Angewandte Chemie International Edition, Год журнала: 2024, Номер 64(3)

Опубликована: Окт. 18, 2024

Abstract The glycosylation of peptides and proteins can significantly impact their intrinsic properties, such as conformation, stability, antigenicity, immunogenicity. Current methods for preparing N‐linked glycopeptides typically rely on amide bond formation, which be limited by the presence reactive functional groups like acids amines. Late‐stage functionalization offers a promising approach to obtaining glycopeptides. In this study, we demonstrate preparation through photoredox‐catalyzed site‐selective Giese addition between N‐glycosyl oxamic acid containing dehydroalanine (Dha) under visible light conditions. Unlike traditional that coupling aspartic glycosylamine, utilizes conjugation N‐glycosylated carbamoyl radicals with Dha, facilitating straightforward modification complex peptides.

Язык: Английский

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Synthesis of Asp-based lactam cyclic peptides using an amide-bonded diaminodiacid to prevent aspartimide formation

Organic & Biomolecular Chemistry, Год журнала: 2024, Номер 22(18), С. 3584 - 3588

Опубликована: Янв. 1, 2024

Asp-based lactam cyclic peptides are considered promising drug candidates. However, using Fmoc solid-phase peptide synthesis (Fmoc-SPPS) for these also causes aspartimide formation, resulting in low yields or even failure to obtain the target peptides. Here, we developed a diaminodiacid containing an amide bond as β-carboxyl-protecting group Asp avoid formation. The practicality of this has been illustrated by cyclo[Lys9,Asp13] KIIIA7-14 and 1Y.

Язык: Английский

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